Plant glucosides possess antioxidative properties due to their ability to scavenge free radicals. Sesame seeds contain a class of these compounds, the sesaminol glucosides. To evaluate their antioxidative activity in vivo, we fed rabbits diets containing 1% cholesterol (Chol) with or without 10% defatted sesame flour (DSF) (containing 1% sesaminol glucosides) for 90 d. We determined the susceptibility of their tissues to oxidation ex vivo as well as serum total cholesterol (TC), phospholipid (PL), triglyceride (TG) and HDL cholesterol (HDL-C) concentrations. Serum TC, HDL-C, PL and TG levels were unaffected by the addition of DSF. The HDL-C in the Chol + DSF group was greater than in the Chol group at 45 d. Both were greater than in the groups that did not consume cholesterol. Liver TC and TG were significantly lower in rabbits fed the diet containing DSF plus 1% cholesterol than in those fed 1% cholesterol alone. Lipid peroxidation activity, measured as 2-thiobarbituric acid reactive substances (TBARS), was lower in the liver (P < 0.05) and serum (P = 0.06) of rabbits fed DSF plus cholesterol than in rabbits fed the cholesterol diet. Although we did not detect sesaminol glucosides in peripheral tissues, we observed abundant quantities of sesaminol in rabbits fed DSF, the principal metabolite. Our findings suggest that feeding DSF to rabbits does not protect cholesterol-induced hypercholesterolemia, but may decrease susceptibility to oxidative stress in rabbits fed cholesterol, perhaps due to the antioxidative activity of sesaminol.